Total parenteral nutrition solution increases bile lithogenicity in rat

The effect of parenteral and enteral nutrition on bile composition was studied in rats. Bile flow, bile fractional composition, bile component output, and lithogenic index were determined in five groups of rats: (A) preoperative control, (B) freely feeding rats infused with normal saline, (C) parenterally fed rats with balanced total parenteral nutrition (TPN) formula (4% amino acids, 22.5% dextrose, 1% Intralipid), (D) constantly intragastrically fed rats with the same TPN formula, and (E) rats fed intragastrically with the same TPN formula but only during 10 hr at night. After 12 days of infusion, bile and blood were collected. There were no differences between the two parenterally and enterally continuously fed groups. Both Groups C and D showed decreased bile flow, decreased bile components output, increased molar percentage concentrations of biliary cholesterol (2.2 ± 0.3 and 1.8 ± 0.1 in Groups C and D, respectively, control, 1.4 ± 0.1), and increased lithogenic index. The cyclically enterally fed group had a normal lithogenic index in the postabsorptive period. Plasma cholesterol and triglycerides were higher in the formula fed groups. There were no changes in plasma liver function tests between the groups. We conclude, therefore, that continuous administration of TPN solution induces an increase in lithogenicity of the bile, independent of the route of administration.     

Effect of female sex hormones on lithogenicity of bile

Effect of female sex hormones on lithogenicity of bile was investigated in an attempt to explain the female preponderance of cholesterol gallstones in man. Estrogen in a form of Estradiol valerate or progesterone in a form of 17α-Hydroxy-progesterone caproate was administered to female dogs oophorectomized to negate influence of endogenous sex hormones from the gonads. Gallbladder bile was puncture aspirated at intervals before, during and after the administration. Lithogenicity of the bile increased markedly during the administration of estrogen. The increase was not so pronounced during the progesterone administration. The increase of lithogenicity is apparently mainly due to increase in the absolute concentration of cholesterol. Differences in the effect of estrogen and progesterone suggest the presence of fluctuation of lithogenicity of bile during the menstrual cycle and pregnancy.     

The differing effects of early and chronic cholelithiasis on hepatic bile lithogenicity

The hypothesis that increasing chronicity of cholelithiasis is associated with a progressive alteration of the enterohepatic circulation, resulting in a decrease in bile salt pool size and reversion of hepatic bile composition to a less lithogenic state, was tested in the prairie dog gallstone model. During the early phases of cholesterol cholelithiasis, both hepatic and gallbladder bile were saturated with cholesterol, and the bile salt pool size was normal. As stones became more chronic, the gallbladder was increasingly removed from the enterohepatic circulation, bile salt recycling increased and the pool size decreased. Despite this decrease in pool size and persistence of lithogenic gallbladder bile, hepatic bile composition reverted to a less lithogenic state. These data suggest that the sequelae of functional cholecystectomy are analogous to those of cholecystectomy. In addition, it appears that the liver and gallbladder interact in a dynamic manner, continually influencing the function of each other.     

Effects of resection or bypass of the distal ileum on the lithogenicity of bile

Changes in the composition and lithogenicity of gallbladder bile after resection and bypass of the distal ileum were investigated in the prairie dog. In animals fed a trace cholesterol diet, both ileal resection and ileal bypass increased the cholesterol saturation of bile. In animals fed a cholesterol-enriched diet, the cholesterol saturation was increased by ileal resection but not by ileal bypass. In the animals fed the trace cholesterol diet, both ileal resection and ileal bypass induced the formation of bilirubinate gallstones.     

Analysis of gallbladder bile in morbid obesity

Thirty-seven per cent of our grossly obese patients selected for gastric bypass had cholesterol gallstones. To document the composition of the biliary lipids prior to weight loss, the bile taken from eleven obese patients at the time of gastric bypass was analyzed and the results compared with those in eleven nonobese patients undergoing elective surgery. There was extreme supersaturation of both gallbladder and hepatic bile in all obese patients. The gallbladder bile of all obese patients fell well outside the micellar zone whereas the bile from all but one of the controls fell within the micellar zone. These data provide biochemical support for the clinical association of obesity and cholesterol gallstone formation and are evidence against the possibility that gastric bypass is a lithogenic operation.     

Bilio-pancreatic bypass for obesity: II. Initial experience in man.

After a successful trial of bilio-pancreatic bypass in dogs, a clinical study has been completed in 18 patients followed for more than 1 year. The operation has been modified to achieve the best weight reduction, and forming the bilio-pancreatic tract of equal length to the alimentary tract with a short common ileal tract, the average weight loss as a percentage of the preoperative body weight was 24.1 +/- 5.4 per cent (mean +/- s.d.) at 6 months and 33.7 +/- 4.1 per cent at 12 months. The only immediate complication was a wound dehiscence, and there were no late complications. Liver function studies showed the absence of hepatic deterioration and liver biopsies showed improvement of liver morphology 1 year after the operation. It is suggested that this procedure may be an alternative to jejuno-ileal bypass in the management of obesity.     

Insulin and hypertension. Relationship to obesity and glucose intolerance in Pima Indians

The relationships among blood pressure, obesity, glucose tolerance, and serum insulin concentration were studied in 2873 Pima Indians aged 18-92 yr (mean 37 yr). Age- and sex-adjusted to the Pima population, the prevalence of hypertension (systolic blood pressure greater than or equal to 160 mmHg, diastolic blood pressure greater than or equal to 95 mmHg, or receiving drug treatment) was 7.1% for subjects with normal glucose tolerance compared with 13.0% for subjects with impaired glucose tolerance (IGT) and 19.8% for those with non-insulin-dependent diabetes mellitus (NIDDM) (P less than 0.001). The prevalence ratio of hypertension was 1.8 (95% confidence interval [CI] 1.2-2.5) for IGT and 2.6 (95% CI 2.0-3.2) for NIDDM compared with normal glucose tolerance, controlled for age, sex, and body mass index (BMI). In logistic regression analysis, hypertension was positively related to age, male sex, BMI, glucose tolerance, and fasting but not 2-h postload serum insulin concentration. Among subjects not taking antihypertensive drugs, however, neither fasting nor 2-h postload serum insulin was significantly related to hypertension. Furthermore, in 2033 subjects receiving neither antihypertensive nor antidiabetic drugs, blood pressure was not significantly correlated to fasting insulin concentration, and 2-h postload serum insulin was negatively correlated with diastolic blood pressure. In conclusion, insulin is not significantly related to blood pressure in Pima Indians not receiving antihypertensive drugs. Higher insulin concentrations in drug-treated hypertensive patients might result from the treatment rather than contribute to the pathogenesis of hypertension. Thus, these data do not support a major role for insulin in determining the occurrence of hypertension or regulation of blood pressure in Pima Indians.     

Relationship of the serum concentration of pancuronium to its neuromuscular activity in man.

The relationship between the time course of the decay of serum concentrations of pancuronium and its neuromuscular blocking effect has been investigated after the intravenous administration of 50, 80 and 100 microgram/kg doses to anesthetized patients. Following administration of these doses, maximal neuromuscular block in the adductor pollicis muscle developed in about 7, 2.5, and 2 minutes and lasted about 20, 40, and 60 minutes, respectively. The times from start of recovery to return of twitch tension to 25, 50, and 75 per cent of control were similar in the different dosage groups, but occurred progressively later with increasing doses. At times of 25, 50, and 75 per cent recovery mean serum concentrations (pooled values) were 0.13 +/- 0.01,0.11 +/- 0.01, and 0.10 +/- 0.01 microgram/ml (+/- SEM), respectively. Neuromuscular transmission to the adductor pollicis muscle started to recover at a mean serum pancuronium concentration of 0.21 +/- 0.03 microgram/ml. The data obtained in this study are in agreement with the experimental and clinical findings of similar studies with d-tubocurarine, and indicate that there is a correlation between the serum concentrations of muscle relaxants and the intensity of their neuromuscular activities.     

Relationship of obesity to postoperative complications after cholecystectomy

A study of 400 patients undergoing cholecystectomy between 1965 and 1969 was undertaken to determine the incidence of complications in obese and nonobese patients. The average complication rate is 42 per cent for female patients weighing less than 175 and 31 per cent for those over 175 pounds. Male patients weighing under 200 have a complication rate of 36 per cent compared to 28 per cent for those more than 200 pounds. There were no patients over 200 pounds who had postoperative cardiac arrhythmias, thrombophlebitis, pulmonary embolus, myocardial infarction, or stress ulcers, whereas several patients in each of the lower weight groups had two or more of these problems. Although obese patients present difficult technical problems, these results demonstrate that obesity per se is not associated with a higher postoperative morbidity or mortality in patients undergoing cholecystectomy.     

The effect of vagotomy on gallbladder function and bile composition in man.

Vagotomy and gastric surgery have been implicated in gallstone formation, although the association remained unproven. Gallbladder function was investigated in 11 patients with a pyloroplasty and truncal vagotomy, 5 with a subtotal gastrectomy, and 16 healthy controls. Gallbladder filing and emptying in response to cholecystokinin (CCK 0.01 U/kg min), when quantitated by 99m-Tc-HIDA cholescintigraphy, did not show any differences between the control and the surgical groups. In each group, over 70% of hepatic activity partitioned into the gallbladder rather than the duodenum, filing the gallbladder at 2.1%/min. Gallbladder emptying began five minutes after initiating the CCK infusion and ejected half of its contents during the next 12 minutes. Biliary lipid compositions was determined in 20 patients who underwent elective pyloroplasty and vagotomy for duodenal ulcer disease. Gallbladder bile collected at surgery was compared to bile-rich duodenal fluid aspirated eight months after recovery from surgery. Cholesterol saturation decreased significantly (p less than 0.05) both in terms of the relative cholesterol content (6.9% leads to 5.2%) and the lithogenic index (1.24 leads to 0.84). To determine if a selective increase in one of the conjugated bile salts could explain this improvement, bile salt composition was analyzed by high pressure liquid chromatography in eight patients and showed no change after surgery. Thus, vagotomy does not adversely affect gallbladder function, but instead improves cholesterol solubility.     

Bile composition and bile cast formation after transplantation of the liver in man.

Transplantation of the liver in man is frequently complicated by biliary fistula and obstruction of the biliary tree by casts, which suggests that the composition of the bile may be abnormal. In part of the present study, bile composition was investigated in three recipients during the first few weeks after transplantation, when a T tube was in place. Supersaturation of bile with cholesterol was found in two patients immediately after surgery and during episodes of acute rejection, but bile was never lithogenic in the third. There was no evidence of bile stasis in the absence of acute rejection and bile viscosity was normal in all three patients throughout the study. Free bile acids and free bilirubin, which are relatively insoluble products of bacterial metabolism, were not present in the bile of any patient. However, chemical analysis of casts found at autopsy in a fourth recipient showed that the major component was free bilirubin. Escherichia coli was grown in cultures of the casts and the organisms were shown to possess glucuronidase activity, thus providing an explanation for the high bilirubin content. There was also some evidence in one case that damage to the bile duct mucosa has led to the precipitation of material upon it, and it is concluded that a number of factors, including infection, supersaturation with cholesterol, and mucosal damage, may be involved in bile case formation after transplantation of the liver.     

Relationship of seminal plasma testosterone and dihydrotestosterone to sperm count and motility in man.

A radioimmunoassay previously described for serum T and DHT was adapted for use in the measurement of these hormones in seminal plasma. The seminal plasmas of 273 semen specimens were assayed for T and DHT concentration. Mean levels of these hormones for various sperm count and sperm motility categories were determined. We found that: (1) the DHT level of the azoospermic group was significantly lower than all other groups; (2) the T level of the group whose mean sperm count exceeded 40 x 10(6)/ml was higher than that of all other groups; (3) the DHT level of the group with absent sperm motility was lower than the level of all other groups; and (4) changes in sperm motility were not accompanied by changes in T levels. We concluded that idiopathic male subfertility as evidenced by oligospermia, azoospermia, and decreased sperm motility may be related to insufficient androgen production due to a primary intratesticular defect.     

Relationship between colorectal liver metastases and CEA levels in gallbladder bile.

While computerized tomographic (CT) scanning and intraoperative exploration are both considered accurate measures of liver involvement with metastatic disease, 10% to 30% of colorectal liver metastases remain undetected. Attempting to improve current methods for detecting colorectal liver metastases, CEA levels in gallbladder bile and serum from patients with known liver metastases were determined. One hundred per cent of patients with single and multiple metastases of various dimensions were observed to have gallbladder bile CEA levels strikingly higher than serum values (4.7 to 259 times greater, p = 0.0009). Linear regression analysis of estimated tumor volume and surface area versus gallbladder bile CEA levels predicted that very small tumors (less than or equal to 1 cm3 in volume) might produce detectable levels (9 to 41 ng/mL) of biliary CEA. For this reason, patients who lack clinical and radiologic evidence of distant metastases at the time of primary colorectal resection but who do have elevated gallbladder bile CEA levels (greater than or equal to 10 ng/mL) are being followed for the appearance of occult hepatic metastases.     

Effect of diet orange soda on urinary lithogenicity

Studies have shown that certain beverages decrease urinary lithogenicity by increasing urine citrate excretion. Diet Sunkist Orange soda had the highest concentration of citrate and total alkali content among 12 diet sodas previously assayed. We studied the effect of Diet Sunkist Orange soda consumption on urinary chemistry. Nine healthy men and women ages 26-54 years completed the study. During the control period, subjects drank 36 oz of water for 3 days in addition to their own, self-selected diet and recorded a food diary. During the study period, the subjects drank three 12-oz cans of Diet Sunkist Orange soda a day instead of water, and replicated their diets from the control period. In each period, the subjects performed 24-h urine collections on days 2 and 3. Urine chemical analysis was performed, including urinary citrate levels and pH. Diet Sunkist Orange soda increased urinary citrate excretion by 60 mg/day, which was not statistically significant (95% CI -75 to 195, P value 0.34). There was no significant change in pH from the control period to the study period (pH: 6.29-6.21; 95% CI: -0.09 to 0.25, P = 0.30). Urine volumes and creatinine excretions were not significantly different between the control and study periods. Despite the relatively high citrate and total alkali content of Diet Sunkist Orange soda, the volume consumed in this study (36 oz per day) did not provide sufficient potential base to significantly alter urine composition in healthy subjects with normocitraturia. The effect of Diet Sunkist Orange soda on urinary chemistry in patients with hypocitraturia and nephrolithiasis is not likely to have a clinically significant effect to prevent calcium or uric acid stones.